Choline acetyltransferase (acetyl CoA:choline O-acetyltransferase, EC 2.3.1.6; synonym: Choline acetylase, Choline O-acetyltransferase; ChAT) is the enzyme responsible for catalyzing the biosynthesis of the neurotransmitter acetylcholine from its precursors, acetyl-coenzyme A (acetyl-CoA) and choline. Acetylcholine was the first neurotransmitter to be reported and plays a pivotal role in such fundamental brain processes as learning, memory and sleep. Acetylcholine functions in the cholinergic neurons of the peripheral and central nervous systems. In the peripheral nervous system acetylcholine stimulates muscle contraction through the neuron-muscular junction and in the central nervous system acetylcholine facilitates learning and short-term memory formation.
There have been reports on choline acetyltransferase from invertabrates including insects as follows. The C. elegans choline acetyl transferase is enriched in synaptic regions of cholinergic neurons (Duerr et al., Midwest Worm Meeting abstract 39). A loss-of-function mutation in C. elegans choline acetyltransferase gene leads to growth arrest at L1 larval stages and death (Yook and Jorgensen, West Coast Worm Meeting abstract 260). A severe reduction-of-function mutation in C. elegans choline acetyltransferase gene leads to slow growth, small body size and an irregular defecation cycle (Rand and Russell, Genetics, 106(2):227-248, 1984). The mutation leads to resistance to acetylcholine esterase inhibitors such as aldicarb or trichlorfon presumably due to undersynthesis of acetylcholine (Rand and Russell, Genetics, 106(2):227-248, 1984).
Choline acetyltransferase is widely distributed in the central nervous system of Drosophila melanogaster throughout all developmental stages (Gorczyca and Hall, J. Neurosci., 7(5): 1361-1369, 1987). Recessive non-conditional loss-of-function mutants for the Drosophila melanogaster choline acetyltransferase gene die at the late embryonic stage (Greenspan, J. Comp. Physiol., 137(1):83-92, 1980). Temperature sensitive reduction-of-function mutants for Drosophila melanogaster choline acetyltransferase become paralysed after incubation at a restrictive temperature (Kitamoto et al., J. Neurobiol., 42(2):161-171, 2000). Using temperature-sensitive loss-of-function mutation at the D. melanogaster choline acetyltransferase locus, it has been shown that normal acethylcholine metabolism is not required for the initial formation of the nervous system but is required for the subsequent maintenance of its structural integrity and function (Chase and Kankel, Dev. Biol., 125(2):361-380, 1988).
Discovery of agricultural chemicals has traditionally been based on a random screening process, often directly testing the effects of specific chemicals on whole organisms, such as insects, fungi and/or plants, and determining biological activity. Once chemical compounds with the appropriate biological activity are discovered, more intense research is required to specifically determine the mode of action or site of action of these compounds at the molecular level, in order to predict safety and environmental load of these compounds.